KR102651768B1 - Fluid systems for conducting analysis - Google Patents

Abstract

A fluid testing system and method of use are provided. The fluid testing system includes a microfluidic channel, a first chamber, and a second chamber. The microfluidic channel has only one port for introduction and/or extraction of fluid through the microfluidic channel. The first chamber is disposed at the distal end of the microfluidic channel. The second chamber is coupled to the fluid channel and aligned such that each opening to the second chamber is aligned substantially parallel to the gravity vector during operation.

Description

Fluid systems for conducting analysis

Embodiments of the present invention relate to the field of clinical diagnostic tools.

Given the complexity of automating molecular testing and immunoassay technologies, there is a lack of products that provide adequate performance for clinical use in near-patient testing settings. Typical molecular testing involves a variety of processes including precise dosing of reagents, sample introduction, lysis of cells to extract DNA or RNA, purification steps, and amplification for subsequent detection. There are central laboratory robotics platforms that automate some of these processes, but for many tests that require short turnaround times, central laboratories cannot provide results within the required time requirements.

However, it is difficult to implement a system in a clinical setting that provides accurate and reliable results at a reasonable cost. Given the complex nature of many molecular testing techniques, results can be prone to errors if testing parameters are not carefully controlled or environmental conditions are less than ideal.

The fact that molecular techniques have superior sensitivity levels at lower concentrations than previous reference methods makes it rather difficult to obtain clinically relevant conclusions, while avoiding erroneous calls with false positives. To minimize these problems, tests should have quantification capabilities, especially when detecting pathogenic microorganisms. Accordingly, it has become increasingly necessary to conduct an array of multiplexed analyzes and tests to integrate sufficient data to draw confident conclusions. Although technologies such as microarray immunoassays offer very high multiplexing capabilities, their main limitation is the slow speed of obtaining results, which often does not have a positive impact on patient management.

A fluid testing system and method of use are provided. Simultaneous fluid control at each testing site reduces testing time and increases the likelihood of obtaining repeatable results between multiple testing sites.

In an embodiment, a fluid testing system includes a microfluidic channel, a first chamber, and a second chamber. The microfluidic channel has only one port for introduction and/or extraction of fluid through the microfluidic channel. The first chamber is disposed at the distal end of the microfluidic channel. The second chamber is coupled to the fluid channel and aligned such that each opening to the second chamber is aligned substantially parallel to the gravity vector during operation.

An exemplary method is described. The method includes flowing liquid through a unique port of a microfluidic channel until the liquid reaches one or more reagents stored within a first chamber coupled to the microfluidic channel. Thereafter, the method includes re-suspending at least a portion of the one or more reagents in the liquid to form the target liquid. The target liquid then flows through the microfluidic channel and away from the first chamber. The method then includes flowing the target liquid back and forth within the microfluidic channel such that the target liquid flows through a second chamber coupled to the microfluidic channel. The method includes reacting at least a portion of the one or more re-suspended reagents in the target liquid with one or more reagents disposed within the second chamber and flowing the target liquid out of the microfluidic channel through a unique port of the microfluidic channel. Includes steps.

In another embodiment, a fluid testing system includes a microfluidic channel, a plurality of chambers, and a chamber disposed at a distal end of the microfluidic channel. The microfluidic channel has only one port for introduction and/or extraction of fluid through the microfluidic channel. Each of the plurality of chambers is coupled to the microfluidic channel in a series arrangement such that each length of the plurality of chambers is aligned substantially parallel to the gravity vector.

The accompanying drawings, which are incorporated herein and form a part of the specification, illustrate embodiments of the invention and, together with the description, are intended to explain the principles of the invention and to enable those skilled in the art to make and use the embodiments. It plays an additional role in order to do so.
1A is a diagram of a test cartridge system according to an embodiment.
1B displays another diagram of a test cartridge system according to an embodiment.
2 shows a fluid testing arrangement, according to an embodiment.
3 shows a plurality of fluid testing arrangements, according to an embodiment.
4A and 4B show diagrams of a fluid testing arrangement, according to some embodiments.
5 shows another fluid testing arrangement, according to an embodiment.
6 shows an exemplary fluid testing method, according to an embodiment.
Embodiments of the present invention will be described with reference to the accompanying drawings.

Although specific configurations and arrangements are described, it should be understood that this is for illustrative purposes only. Those skilled in the art will recognize that other configurations and arrangements may be used without departing from the spirit and scope of the invention. It will be apparent to those skilled in the art that the present invention can also be used in a variety of other applications.

Reference in the specification to “one embodiment,” “an embodiment,” “an exemplary embodiment,” etc. means that the described embodiment may include particular features, structures, or characteristics, but that all embodiments do not include such particular features, structures, or characteristics. It should be noted that it may not necessarily include or characteristics. Furthermore, such phrases are not necessarily referring to the same embodiment. Additionally, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is not common in the art to implement such feature, structure, or characteristic in conjunction with other embodiments, whether explicitly described or not. It will be presented that it is included in the knowledge of the technician.

Some embodiments described herein relate to microfluidic arrays integrated into test cartridge systems for conducting various molecular tests, such as immunoassays, PCR, DNA hybridization, etc. In embodiments, a test cartridge integrates all components necessary to conduct such testing into a single, disposable package. The test cartridge may be configured to be analyzed by an external measurement system that provides data related to the reactions occurring within the test cartridge. In an embodiment, the test cartridge includes a plurality of testing chambers with a transparent window for conducting optical detection into each testing chamber.

In one example, a single test cartridge can be used to perform an array of immunoassays with a given sample. The test cartridge contains all necessary buffers, reagents and labels held within a sealed chamber integrated into the cartridge to conduct an immunoassay.

One of the main limitations of molecular diagnostic instruments is problems associated with contamination, such as cross-contamination and carry-over contamination. Embodiments described herein, by design, substantially prevent contamination of samples to the instrument.

In one embodiment, the test cartridge provides self-contained liquid or dried reagents that are sealed during the manufacturing process. The reagents and introduced samples do not come into contact with the environment or any part of the apparatus. This feature of the test cartridge is also important to many laboratories and hospitals in safely disposing of the product after use.

To conduct an array of tests, the test cartridge includes a plurality of fluid channels as well as a plurality of testing chambers. Fluidic channels can be designed to connect various testing chambers and to deliver liquid to different parts of the test cartridge. The fluidic channel can be designed to assist in conducting immunoassays within connecting chambers along the fluidic channel.

Some details related to the components of the test cartridge system are explained with reference to the drawings. The illustration of each physical component is not meant to be limiting, and given the description herein, those skilled in the art will recognize how to rearrange or otherwise modify any component without departing from the scope and spirit of the invention. You must understand that you will be able to recognize it. Additional details regarding the test cartridge system can be found in co-pending U.S. application Ser. No. 13/836,845, the disclosure of which is incorporated herein by reference in its entirety.

1A shows an example test cartridge system 100, according to an embodiment. Test cartridge system 100 includes a cartridge housing 102 that can accommodate various fluid chambers, channels, and reservoirs. A sample may be introduced into cartridge housing 102 through sample port 104, depending on the embodiment. In examples, sample port 104 receives a solid, semi-solid, or liquid sample. Sample port 104 may also be designed to receive the needle of a syringe for injecting a sample into a chamber or fluid channel within cartridge housing 102. In another embodiment, cartridge housing 102 includes more than one inlet for introducing a sample. Additional details regarding the various chambers and channels of cartridge system 100 can be found in co-pending U.S. application Ser. No. 13/836,845.

Depending on the embodiment, the cartridge system 100 may include a delivery chamber that moves laterally along a guide 106 within the cartridge housing 102 . This delivery chamber may be used to align various fluid ports with the delivery chamber and to control the movement of fluid throughout the various fluid channels and chambers of cartridge system 100.

Cartridge system 100 includes one or more through-holes 108 according to an embodiment. Through-holes 108 may be located on the thin portion of cartridge system 100. In one example, this thin portion is located away from many of the fluid chambers within cartridge housing 102. Through-hole 108 allows various reagents to be placed within through-hole 108 to effectively “plug” the hole. Accordingly, the reagent can be placed on a small plug that fits snugly within the through-hole 108. Examples of reagents may include immobilized antibodies, proteins, enzymes, single-stranded or double-stranded DNA or RNA. To ensure a substantially leak-proof fitting, a gasket seal may be used around the edge of the plug. Additional details regarding this plug are described below with reference to FIG. 4 .

FIG. 1B shows a rear view of an example test cartridge system 100, according to an embodiment. Numerous fluid channels are visible within cartridge housing 102. In one example, this fluid channel is a microfluidic channel, and fluid flows in a laminar flow regime through the channel. Accordingly, the dimensions of the microfluidic channel may have a cross-section of, for example, less than 5 mm ² , less than 1 mm ² , less than 10,000 μm ² , less than 5,000 μm ² , less than 1,000 μm ² , or less than 500 μm ² .

Depending on the embodiment, several fluid testing areas are integrated within cartridge housing 102. For example, testing area 110 may include a plurality of fluid testing arrangements, each fluid testing arrangement aligned with one of the through-holes 108 from a different side of test cartridge 100. It has an opening 112 that is. Accordingly, each of the openings 112, when plugged with reagents, forms a testing chamber for a variety of biological and chemical tests. These tests may include immunoassays, enzyme interactions, cellular responses, or DNA hybridization, to name just a few. Other tests that may be performed will be apparent to those skilled in the art given the disclosure herein. Additional details regarding each testing arrangement shown within testing area 110 are described below with reference to FIG. 2 .

Another fluid region 114 includes a plurality of chambers connected in a series arrangement, according to an embodiment. These chambers can be used for dilution and to provide precise dosage concentrations to other chambers and fluidic channels within the system. Additional details regarding the depicted fluid region 114 are described below with reference to FIG. 5 . Various other fluid channels 116 are also shown, for directing fluid between the various chambers within the cartridge housing 102 and for directing fluid to/from the various chambers to the testing area 110 or the fluid area 114. ) can be used to guide you to any of the channels shown in ).

2 shows an example of a fluid testing arrangement 200, according to an embodiment. According to one example, the gravity vector is also shown to provide an orientation in which the fluid testing arrangement 200 is designed to be used for maximum effectiveness. Other orientations may also be possible, but may lead to the formation of unwanted bubbles within the channel.

According to an embodiment, the fluid testing arrangement 200 includes a microfluidic channel 202 having only one port 204. The other end of microfluidic channel 202 terminates in a closed chamber 216. This closed chamber acts as a reservoir for air trapped within the microfluidic channel 202 when fluid is pushed through the microfluidic channel 202 through port 204. Including a closed chamber 216 replaces the need to use a vent that could allow air to escape the system. Not having a vent offers advantages, such as reduced potential for leaks and contamination.

Microfluidic channel 202 may have one or more chambers or enlarged regions disposed along the length of microfluidic channel 202. For example, microfluidic channel 202 may include one or more channel enlargements 206, such as 206a and 206b. Channel enlargements 206a and 206b may act as liquid sensing regions. Accordingly, channel enlargements 206a and 206b may be utilized with one or more external optical probes to determine whether liquid is present within channel enlargements 206a and 206b. These decisions can be used to activate other functions of test cartridge system 100. In other embodiments, channel enlargements 206a and 206b may include integrated sensors, such as patterned resistance sensors, to indicate the presence or flow rate of fluid.

Microfluidic channel 202 may also be coupled with mixing chamber 208. In an embodiment, mixing chamber 208 has a larger cross-sectional dimension than microfluidic channel 202. This large cross-sectional dimension may be selected such that the fluid regime within mixing chamber 208 is no longer laminar but turbulent. By varying the pressure applied to the port 204, the sample solution can be moved back and forth within the mixing chamber 208, thereby providing passive mixing of the fluids. Depending on the embodiment, the mixing chamber 208 is aligned such that the opening to the mixing chamber 208 is substantially aligned with the gravity vector. This alignment helps reduce the creation of bubbles in the chamber when fluids are mixed.

Microfluidic channel 202 also includes testing chamber 210. In one example, testing chamber 210 is located further downstream than mixing chamber 208 within microfluidic channel 202. Testing chamber 210 may be aligned over one of the through-holes 108 shown in FIG. 1A. Accordingly, reagents may be placed into testing chamber 210 by “plugging” one side of testing chamber 210 using a plug insert as shown in FIG. 4 . The geometry of testing chamber 210 allows for a large surface area for interaction with the various reagents within testing chamber 210. For example, the diameter of testing chamber 210 is substantially similar to the diameter of one of a standard-sized 96-well plate, 24-well plate, 48-well plate, or 384-well plate. may be chosen to do so. The fluid volume within testing chamber 210 may be less than 50 μL. In one example, the fluid volume within testing chamber 210 is 10 to 30 μL. The volume of the testing chamber 210 can be designed to be large enough to be completely filled with 50 μL sample solution. In an embodiment, the opening of testing chamber 210 is aligned substantially parallel to the gravity vector. Once the openings are aligned in this way, the chamber can be positioned along the fluid channel so that fluid can fill the chamber from the bottom upward. By filling the testing chamber 210 in this manner, the generation of air bubbles can be reduced. In one embodiment, testing chamber 210 may include a plurality of beads to increase surface area for reagent interaction. By varying the pressure applied to the port 204, the sample solution can be moved back and forth within the testing chamber 210, thereby maximizing the interaction between the reagents fixed within the testing chamber 210 and the reagents in the sample solution. can do.

A large cross-sectional dimension of testing chamber 210 may be selected such that the fluid regime within testing chamber 210 is no longer laminar but turbulent. This turbulent flow increases the rate of reaction between the fixed reagent in the testing chamber 210 and the reagent in solution. Depending on the embodiment, the testing chamber 210 is aligned such that the opening to the testing chamber 210 is substantially aligned with the gravity vector. This alignment helps reduce the creation of air bubbles within the chamber as the sample solution is moved back and forth within the testing chamber 210.

Detection of reagent interactions within the testing chamber 210 may be accomplished using an external light source and photodetector coupled to an analyzer disposed within the test cartridge system 100. Accordingly, any walls or covers of testing chamber 210 may be transparent to allow optical detection. In one example, the photodetector measures absorbance through the liquid in testing chamber 210 at one or more wavelengths. In another example, a photodetector measures a fluorescent signal generated from a fluorescent compound within testing chamber 210. In an embodiment, fluorescence measurements are taken from underneath the testing chamber 210. Testing chamber 210 may be configured for other detection means, such as electrochemical, electromechanical, surface plasmon resonance, time-resolved fluorescence, etc.

Storage chamber 212 may be located along microfluidic channel 202 and downstream of testing chamber 210. Storage chamber 212 may contain dry chemicals, such as frozen or lyophilized analytes. In another example, storage chamber 212 may contain dry reagents 214 or biological samples. Biological samples may be freeze-dried within storage chamber 212. Such biological or chemical compounds may be stored within storage chamber 212 for extended periods of time until use. According to one embodiment, the dimensions of the storage chamber 212 may be specifically designed to fit the size of the dried reagent 214 (such as dried chemical beads), on the order of a few millimeters in diameter. In one example, fluid drawn toward storage chamber 212 mixes with dried reagents 214 within the fluid and re-suspends those reagents. The liquid with resuspended reagents can then be pulled back toward the testing chamber 210 for analysis.

Several chambers along microfluidic channel 202 may be strategically placed depending on the application and test being conducted. For example, in the arrangement shown in FIG. 2, buffer liquid is forced, by applied positive pressure, through port 204 and all around storage chamber 212, thereby reducing dried reagent 214 to a buffer solution. re-suspend within it and thereby form a test solution. Next, the test solution can be pulled back through the microfluidic channel 202 by negative pressure applied at port 204, or by releasing the previously applied positive pressure. The test solution may be returned all the way to the channel enlargement 206a. After this, the fluid may be forced back and forth between the channel enlargement 206a and the storage chamber 212 a number of times, passing both the mixing chamber 208 and the testing chamber 210. In this way, the fluid continues to mix through mixing chamber 208 while interacting with captured reagents in testing chamber 210. In the example of an immunoassay, the capture antibody is immobilized within the testing chamber 210 while the protein present in the test solution is introduced to the capture antibody. The binding reaction can produce a positive test result (can produce a fluorescent signal). Once a test solution has been introduced through testing chamber 210 and sufficient time has passed, the solution can be pulled out of port 204 and another cleaning solution introduced (e.g., to eliminate false positives). Any unbound material within testing chamber 210 may be cleaned. The cleaning solution can be introduced onto the analyte in testing chamber 210 without having to pass through storage chamber 212. This is advantageous because it prevents the possibility of any dry chemicals remaining within the storage chamber 212 being re-suspended. It should be understood that this is just one example use of fluid testing arrangement 200, and that the arrangement of the chambers may vary based on the application.

3 shows multiple fluid test arrangements connected to the same input fluid channel 302, according to an embodiment. Input fluid channel 302 includes one port 304 for introduction and discharge of liquid and for application or release of pressure to the liquid. Input fluid channel 302 may be coupled to a fluid junction 306 where one fluid channel is divided into a plurality of fluid channels. In one example, each of the plurality of fluid channels supplies its own testing arrangement 308. Although only three testing arrangements 308 are shown connected to input fluid channel 302, it should be understood that any number and type of fluid testing arrangements may be coupled to input fluid channel 302.

Storage chambers 310 within each testing arrangement 308 may contain different concentrations of reagents or different reagents all originating from other storage chambers 310 . Similarly, the reagents placed within the testing chambers 312 within each testing arrangement 308 may include different concentrations of reagents or different reagents all originating from different testing chambers 312. In this way, multiplexed arrays of experiments can be conducted from the same input fluidic channel 302.

4A and 4B illustrate a process for placing a reagent insert 402 within a testing chamber 210 that is part of a fluid testing arrangement 200, according to an embodiment. It should be understood that the drawings of FIGS. 4A and 4B are not intended to limit the design of the fluidic system in any way, but are provided merely to illustrate how reagent insert 402 may be used.

Reagent insert 402 is molded to fit comfortably within hole 404 on the rear side of housing 401, while hole 404 is aligned within testing chamber 210 on the front side of housing 401. The reagent insert may include a gasket seal around its edges to help prevent leakage of any fluid after being placed within the hole 404. One side of reagent insert 402 may contain various reagents for use within testing chamber 210. For example, reagent insert 402 can include a surface with a specific capture antibody to be used in an immunoassay. The reagent may be lyophilized on the surface of the reagent insert 402 or may be coated on the top of the insert 402. Insert 402 may include a protective coating that dissolves when contacted with fluid. According to one embodiment, reagent insert 402 may be removed from hole 404 at any time to be replaced with another reagent insert. Reagent insert 402 may be secured to the cartridge by any retaining structure or adhesive, as will be understood by a person skilled in the art.

5 shows another fluid arrangement 500, according to an embodiment. Microfluidic channel 502 includes only one port 504, coupled between chambers 506 arranged in series along microfluidic channel 502. In one example, the microfluidic channel 502 follows a serpentine path with chambers 506 aligned horizontally along that path, as shown in FIG. 5 . Each individual chamber can be formed having a length that is greater than the width, with such length being aligned substantially parallel to the gravity vector as shown. Additionally, the openings at the top and bottom of each chamber 506 are aligned with the gravity vector. Depending on the embodiment, microfluidic channel 502 terminates in an enclosed chamber 510. Enclosed chamber 510 may be designed as a reservoir for air forced through microfluidic channel 502 when liquid enters through port 504. Each chamber of the plurality of chambers may have a fluid volume of less than 250 μl, less than 100 μl, or less than 50 μl.

Microfluidic channel 502 may also include a plurality of channel enlargements 508a - 508e. Channel enlargers 508a-508e may function in a similar manner as described above with reference to FIGS. 2 and 3. Channel enlargements 508a - 508e may be arranged along the microfluidic channel 502 such that the number of chambers 506 between adjacent channel enlargements is variable. In this context, adjacent channel enlargements describe any two channel enlargements along the path of the microfluidic channel 502 that do not have another channel enlargement between them. In other words, exemplary patterns of channel enlargement 508 (CE) and chamber 506 (CH) as fluid moves down microfluidic channel 502 toward enclosed chamber 510 are: CE; CH; CE; CH; CH; CE; CH; CH; CH; CH; CE; CH; CH; CH; CH; It's CE.

Depending on the embodiment, fluid arrangement 500 may be used to perform dilution, reagent administration, and various mixing steps. Chamber 506 may also be used to store various fluids for later use. For example, reagent solutions of different concentrations may be present, with the concentration increasing for each chamber to the right, with the lowest concentration in the leftmost chamber and the highest concentration in the rightmost chamber of chamber 506. It may be stored within chamber 506. Alternatively, the highest concentration may be in the leftmost chamber of chamber 506, with the concentration decreasing for each chamber to the right until the lowest concentration is in the rightmost chamber of chamber 506. It can be.

In one example, first liquid enters through port 504 until it reaches channel enlargement 508a. The presence of the first liquid is determined in the channel expansion unit 508a using a liquid sensor. When it is determined that the first liquid is in the channel enlargement 508a, a signal may be transmitted to stop the flow of the first liquid. The second liquid then flows through port 504 until it reaches another channel enlargement (any one of 508b through 508e) further downstream. This can be repeated with other liquids after the second liquid. In this way, two or more liquids of known concentration can be stored within chamber 506.

FIG. 6 is a flow diagram illustrating a method 600 using a fluid testing arrangement, according to an embodiment. It should be understood that the steps depicted in method 600 are not comprehensive and that other steps may also be practiced without departing from the scope or spirit of the invention.

At block 602, depending on the embodiment, liquid is flowed through the fluidic channel (e.g., by applied pressure) until it reaches the reagent stored within the storage chamber. Liquid can enter the fluid channel through one port, which is the only input/output port of the fluid channel. The reagent may be, for example, any dried reagent intended to be dissolved by a liquid, a lyophilized reagent, or a reagent contained within a pellet. These steps may describe the liquid moving through the microfluidic channel 202 until it reaches the dried reagent 214 in the storage chamber 212, as shown in FIG. 2.

At block 604, the reagent is re-suspended in the liquid. In one example, the liquid may be a buffer solution that has properties that allow the reagent to dissolve in the buffer and remain stable in the buffer. Once the reagents are mostly dissolved, the liquid can be referred to as the target liquid for the remaining steps in the process.

At block 606, the target liquid is flowed away from the storage chamber. In the example shown in Figure 2, the target liquid may be pulled back through the microfluidic channel and away from the storage chamber 212.

At block 608, the target liquid flows back and forth within the fluidic channel such that the target liquid intersects through the testing chamber, depending on the embodiment. This testing chamber may contain a set of different reagents that react with the reagents re-suspended in the target liquid. The target liquid may be moved back and forth solely within the testing chamber, or through other parts of the fluid system as well. For example, and referring to Figure 2, the target liquid may be moved back and forth between channel enlargements 206a and 206b such that the target liquid traverses both testing chamber 210 and mixing chamber 208. Passing the liquid through the mixing chamber 208 multiple times may be an optional step to provide better mixing of the re-suspended reagents in the target liquid. Liquid may also move back and forth between channel enlargement 206a and storage chamber 212.

At block 610, the reagent in the target liquid reacts with the reagent in the second chamber. This process occurs simultaneously with the movement of liquid described above at block 608. For immunoassays, a capture antibody or antigen sample can be immobilized within the second chamber while a target antibody/antigen can be bound to the capture antibody/antigen. Other reactions may include enzymatic reactions that result in color (e.g., absorbance) changes or reactions involving bioluminescent proteins.

At block 612, depending on the embodiment, the target liquid is flowed out of the fluid channel by a single port. The target liquid can be removed through applying negative pressure to a single port, thereby pulling the target liquid outward. Following removal of the target liquid, another liquid may be introduced through the fluidic system. For example, several cleaning liquids can be introduced and flowed through the second chamber to clean and remove any unbound material.

The foregoing description of specific embodiments will fully reveal the general nature of the invention, so that others, by applying the knowledge of a person skilled in the relevant art, can do so without departing from the general concept of the invention. One may easily modify and/or adapt such specific embodiments for a variety of applications without experimentation. Accordingly, such adaptations and modifications are intended to be included within the meaning and scope of equivalents of the disclosed embodiments based on the teachings and guidance presented herein. It will be understood that the phrases and phrases herein are for the purpose of description and not of limitation, and that the terms and phrases herein may therefore be interpreted by those skilled in the art in light of the teachings and guidelines.

Embodiments of the invention have been described above with the aid of functional building blocks that illustrate implementations of specific functions and their relationships. The boundaries of these functional building blocks are arbitrarily defined herein for convenience of explanation. Alternative boundaries may be defined, as long as certain functions and relationships can be implemented appropriately.

The 'Summary' and 'Summary' sections may describe one or more exemplary embodiments, but not all exemplary embodiments, of the invention as contemplated by the inventor(s), and may therefore describe the invention and the appended claims. It is not intended to limit the scope in any way.

The breadth and scope of the present invention should not be limited by any of the foregoing exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.

Claims (29)

The fluid testing arrangement is:
As a housing,
Microfluidic channel with only one port;
a first chamber disposed at the distal end of the microfluidic channel; and
a housing coupled to the microfluidic channel, the housing comprising a second chamber arranged in series with the first chamber; and
A reagent insert having one or more reagents on a surface of the reagent insert, the reagent insert being molded to fit within a through-hole through a rear surface of the housing, the through-hole being aligned within the second chamber.
A fluid testing arrangement comprising: According to paragraph 1,
A fluid testing arrangement further comprising one or more liquid sensing regions coupled to the microfluidic channel. According to paragraph 1,
A fluid testing arrangement coupled to the microfluidic channel and further comprising a third chamber configured to contain one or more reagents. According to paragraph 3,
A fluid testing arrangement wherein the third chamber is sized to contain freeze-dried pellets containing one or more reagents. According to paragraph 1,
A fluid testing arrangement, wherein one or more reagents include a capture antibody. According to paragraph 1,
A fluid testing arrangement, wherein one or more reagents comprise single-stranded or double-stranded DNA. According to paragraph 1,
A fluid testing arrangement, wherein the second chamber includes at least one transparent wall to allow optical interrogation. According to paragraph 1,
A fluid testing arrangement, wherein the second chamber includes a plurality of beads. According to paragraph 1,
A fluid testing arrangement wherein the microfluidic channel is configured to be divided into a plurality of microfluidic channels, each of the plurality of microfluidic channels coupled to a respective first chamber, a respective second chamber, and a respective third chamber. . According to paragraph 1,
A fluid testing arrangement further comprising a third chamber, the third chamber coupled to the microfluidic channel and configured to mix fluid moving through the third chamber. According to paragraph 1,
A fluid testing arrangement, wherein the second chamber has a fluid volume of less than 50 microliters. Here's how:
flowing the liquid through the unique port of the fluidic channel until the liquid reaches one or more reagents stored in the first chamber coupled to the fluidic channel;
re-suspending at least a portion of the one or more reagents within the liquid to form a target liquid;
flowing a target liquid through the fluidic channel and away from the first chamber;
flowing the target liquid back and forth within the fluid channel, such that the target liquid flows through a second chamber coupled to the fluid channel;
reacting at least a portion of the one or more re-suspended reagents in the target liquid with one or more reagents immobilized in the second chamber; and
A method comprising flowing the target liquid out of the fluidic channel through a unique port of the fluidic channel. According to clause 12,
The method of claim 1, wherein flowing the target liquid back and forth within the fluidic channel includes flowing the target liquid back and forth between two locations in the fluidic channel. According to clause 12,
The method further comprising detecting the presence of liquid at each of two locations in the fluid channel. According to clause 12,
The method of claim 1, wherein flowing the target liquid back and forth within the fluid channel includes flowing the target liquid through the third chamber and mixing the target liquid as it flows through the third chamber. According to clause 12,
The method further comprising measuring an optical signal from the second chamber, wherein the optical signal is associated with a concentration of one or more re-suspended reagents in the second chamber. According to clause 12,
flowing a second liquid through a unique port of the fluid channel;
flowing the second liquid back and forth within the fluid channel such that the second liquid flows through the second chamber;
The method further comprising flowing the second liquid out of the fluid channel through a unique port of the fluid channel. According to clause 17,
A method wherein the second liquid is a wash buffer. According to clause 12,
The method of claim 1, wherein reacting comprises combining at least a portion of the one or more re-suspended reagents in the target liquid with one or more reagents disposed in the second chamber. According to paragraph 1,
a second microfluidic channel with only one port;
a plurality of chambers, each chamber of the plurality of chambers coupled to the second microfluidic channel in a series arrangement such that the longest lengths of each of the plurality of chambers are aligned parallel to each other; and
further comprising a chamber disposed at a distal end of the second microfluidic channel,
A fluid testing arrangement, wherein at least a portion of the second microfluidic channels follow a serpentine path, and each chamber of the plurality of chambers is arranged along a serpentine path. According to clause 20,
A fluid testing arrangement, wherein each chamber of the plurality of chambers has a fluid volume of less than 50 microliters. According to clause 20,
A fluid testing arrangement, further comprising a plurality of liquid sensing regions along the second microfluidic channel. According to clause 22,
A fluid testing arrangement, wherein the plurality of liquid sensing regions are arranged along the second microfluidic channel in a given pattern with the plurality of chambers. According to clause 23,
A fluid testing arrangement, wherein a given pattern includes different numbers of a plurality of chambers between adjacent ones of the liquid sensing regions. delete delete delete delete delete

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